Cancer is the second leading cause of death in the world. Each year, cancer kills over 500 thousand people in the United States alone (National Cancer Institute). Current cancer diagnosis methods usually involve two medical procedures. The first procedure is a wide-area surveillance over the tissue, for example: mammogram, colposcopy, palpation, or visual examination. When warning signs are present, biopsy is performed on the suspicious tissue sites. However, many forms of precancerous and early cancerous lesions are difficult to detect using these traditional surveillance procedures. Therefore, there is a need for wide-area surveillance systems capable of precancer detection.
Medical imaging modalities such as mammography and colposcopy have proven vitally important for cancer diagnosis. So far, the majority of imaging modalities focus on tissue structure or anatomy, which is not sufficient for detecting precancers at their earliest stages. Biochemical and subcellular morphological changes have been shown to accompany precancer development. Thus, it is most beneficial to develop new cancer imaging modalities that provide tissue biochemical and morphological information. Several new optical imaging modalities show great promise:
Confocal microscopy eliminates multiple scattering in turbid samples, producing thin section images with high resolution and contrast. The images produced are due to light scattered backwards at interfaces of different refractive index. Multiple scattered light is rejected by means of a pinhole, which selects only light traveling in straight-line paths. The location and size of the pinhole, among other variables, determine the depth and lateral resolution of the system.
Optical coherence tomography (OCT) utilizes the coherence properties of light to obtain cross sectional images of scattering media such as living tissue. This technique employs low coherence light (i.e. light with a short coherence length) in a Michelson interferometer. The specimen is placed at the end of the sample arm. Back-scattered light is combined with light returning from the mirror in the reference arm. Constructive interference occurs only when the distance to a scattering interface in the sample matches that to the reference mirror to within the coherence length. Depth is probed by scanning the reference mirror position and detecting the envelope of the interference signal. Cross-sectional images can be built up from multiple axial scans at different transverse positions in the sample. As with confocal microscopy, image formation is again due to refractive index change.
Several groups have used polarized light to image superficial tissues including using polarized light to enhance contrast in skin images by separating the specular and multiple-scattered components of light emerging from the skin surface or polarized gating can enhance the images of surface and sub-surface structures in biological tissues.
Fluorescence is induced by the excitation of fluorophores in the tissue, usually with blue or ultraviolet (UV) light. Therefore, fluorescence contains information about fluorophore concentration in the tissue. Two-photon microscopy (TPM) is capable of imaging fluorophores deep within a tissue sample. Tissue auto-fluorescence has also been used to detect neoplastic growths in-vivo.
Medical imaging modalities for precancer diagnosis can also employ spectroscopy. Fluorescence spectroscopy imaging systems have been used for detecting cervical intraepithelial neoplasia and combined fluorescence and reflectance spectroscopy methods are complementary for cancer diagnosis, making the use of the two techniques together more diagnostic than the use of either method separately.